The goal of this proposal is to develop new and more effective treatment modalities for patients harboring nervous system tumors. Two major areas of research will be undertaken. I. The Problem of Increased Intracranial Pressure and Cerebral Edema in Animals Bearing Transplanted Brain Tumors will be studied utilizing an intracerebrally implanted ependymoblastoma in the mouse and an intracerebrally implanted glioma in the rat. Using radioactive markers, the source of cerebral edema surrounding brain tumors will be sought on the hypothesis that edema fluid comes from blood vessels within the tumor and diffuses into the surrounding brain. The effect of corticosteroid hormones on the edema and on lysosomal enzymes and ATPase will be studied as will the relationship of steroids and radiation therapy on intrancranial pressure in animals harboring tumors. II. The Development and Investigation of Three New Animal Models of Human Nervous System Cancer. (a) Meningeal Carcinomatosis: A model for meningeal carcinomatosis, an increasingly important problem in humans will be developed by intraventricular injection of tumor cells. The pathophysiology of this model will be studied in parallel with studies on the distribution of intrathecally administered drugs since such administration is currently the best method for treating this disease. (b) Epidural Spinal Cord Compression: A model of epidural spinal cord compression will be developed by transplanting tumors into the neck region of mice and rats and permitting the tumors to invade the epidural space. The pathophysiology of this disease, the occurrence of spinal cord edema and the effects on the edema of corticosteroids, radiation therapy and osmotic agents will be tested. (c) Cerebral Metastases: A search for spontaneous cerebral metastases in systemic animal tumors will be undertaken. Additionally, efforts will be made to develop intracerebral metastatic disease by injection of single cell suspensions of animal tumors into the carotid arteries of mice and rats.